An Hitachi H-7000-3DT Transmission Electron Microscope (TEM) is requested as a shared instrument for a Major User Group comprised of seven investigators from the Departments of Medicine and Physiology at Jefferson Medical College. Six of the seven investigators have funded Public Health Service peer-reviewed research grants (six RO1s, one R29 and one project in a Program Project) which utilize high resolution TEM as an integral tool. Moreover, four additional new RO1s are currently under review. Every funded and pending project depends upon ultrastructural image analysis; some projects more than others. These projects will require 100% of the usage of the proposed shared instrument. The Hitachi H-7000-3DT is a sophisticated, high resolution (0.204 mn) instrument that meets every need of the Major User Group. It provides inherently better contrast than other TEMs because of a 5-stage lens system, a specifically designed column liner that removes electron spray from and around the primary beam, and an auto-adjusting anode that optimizes illumination at all accelerating voltages (10-125 kV). Its computerized design provides unequaled ease of operation in a system that allows both experienced and novice users to optimize observation and analysis of biological specimens. The CCD Integrated TV System provides immediate interface to most image analysis and storage systems, including VCR and optical disc recording. Significant benefits of the TV system are improved signal to noise ratio, enhanced image contrast, and dimensional measurement (i.e., morphometry, stereology, 3-D reconstruction). An instrument with these specific capabilities does NOT exist at Jefferson Medical College. TEMS currently at this institution do not meet the specific needs of the major User Group and availability on a similar (but not comparable) instrument is severely limited. Dr. Albertine, the Principal Investigator, is a professional electron microscopists who will be responsible for operation and maintenance of the shared instrument. Working with Dr. Albertine are two full-time microscopy technicians. The Internal Advisory Committee will be composed of three individuals: Dr. Albertine, Dr. Siegman (both are Major Users) and Dr. Martinez-Hernandez (an "outside" expert in electron microscopy who directs a TEM facility in the Department of Pathology). Strong institutional support is expressed by commitments of space, funds to cover the service contract, and funding mechanisms for new investigators. The proposed shared instrument will broaden and enhance the overall research efforts of the Major User Group by providing a dedicated, high performance. TEM equipped for real-time, interactive ultrastructural image analysis. Existing TEMS at our disposal do not allow us to conduct our research efforts in this manner.